Polyarteritis Nodosa - PAN
- Diagnosis
- Algorithms
- Background
- Pediatrics
- Lab Tests
- References
- Related Topics
Indications for Testing
- Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)
Laboratory Testing
- Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
- CBC – rule out infection
- Urinalysis (UA) – hematuria, proteinuria, red blood cell casts
- C-reactive protein (CRP)
- Preferred test to detect inflammatory processes (Choosing Wisely: 5 Things Physicians and Patients Should Question, 2015; American Society for Clinical Pathology)
- Frequently elevated
- If CRP not available, order erythrocyte sedimentation rate (ESR)
- Testing to consider to rule out other diagnoses
- ANCA – rarely positive, to rule out ANCA-associated vasculitis
- Hepatitis B surface antigen – rule out concomitant chronic hepatitis
- ANA – rule out connective tissue diseases
- Antiglomerular basement membrane antibodies – rule out an antiglomerular basement membrane disease (anti-GBM)
Histology
- Small- and medium-size artery necrotizing vasculitis with absence of glomerulonephritis
- Arterioles, capillaries and/or venules – most affected
- Immunofluorescence fails to demonstrate complement or immunoglobulin in vessel walls
Imaging studies
- Angiography – microaneurysms and stenoses of medium vessels
Differential Diagnosis
- Alport syndrome
- Connective tissue diseases
- Anti-GBM disease (Goodpasture syndrome)
- Vasculitis
- Infection
- Cryoglobulinemia
- Malignancy
Polyarteritis nodosa (PAN) is a necrotizing vasculitis resulting in aneurysmal formation and organ infarction. It is categorized as a medium vessel vasculitis (Chapel Hill, 2012).
Epidemiology
- Incidence –16-25/1,000,000 for systemic vasculitis as a group (includes eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa and granulomatosis with polyangiitis)
- Age – peak onset in 50s
- Sex – M:F, equal
Risk Factors
- Chronic hepatitis B
Clinical Presentation
- Constitutional – fever, malaise, weight loss, arthralgias
- Cardiovascular – coronary artery disease
- Dermatological – vascular purpura, livedo reticularis, lower extremity ulcers, subcutaneous ulcers
- Gastrointestinal – nonspecific abdominal pain, gastrointestinal bleeding, bowel perforation
- Neurological – mononeuropathy multiplex
- Renal – renovascular hypertension, vascular nephropathy
Clinical Background
Epidemiology
- Age – peak is 9-11 years
- Sex – M<F, slight
Clinical Presentation
- Tends to be a more limited disorder than in adults
- Constitutional – fever, malaise, weight loss
- Musculoskeletal – arthritis/arthralgia, myositis, myalgia
- Renal – vascular hypertension, hematuria, proteinuria
- Neurological – peripheral neuropathy
- Gastrointestinal – nonspecific abdominal pain
- Dermatological – livedo reticularis, skin nodules, skin infections
Diagnosis
Indications for testing
-
Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)
Laboratory testing
- Nonspecific testing
- CBC – anemia, leukocytosis, thrombocytoses
- C-reactive protein (CRP)
- Preferred test to detect inflammatory processes (Choosing Wisely: 5 Things Physicians and Patients Should Question, 2015; American Society for Clinical Pathology)
- Usually elevated
- If CRP not available, order erythrocyte sedimentation rate (ESR)
- Urinalysis (UA) – proteinuria, hematuria, red cell casts
- Electrolytes – increases in BUN/Cr not uncommon
- ANCA – rarely positive
Histology
- Small- and medium-size artery necrotizing vasculitis in the absence of glomerulonephritis
- Vasculitis in arterioles, capillaries or venules
- Immunofluorescence fails to demonstrate complement or immunoglobulin in vessel walls
Imaging studies
- Angiography – microaneurysms and stenoses of medium vessels
Differential Diagnosis
- Infection
- Vasculitis
- Microscopic polyangiitis
- Kawasaki disease
- IgA vasculitis
- Connective tissue diseases
- Alport syndrome
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential
Identify anemia, leukocytosis, thrombocytoses
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry
Preferred test to detect inflammatory processes
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy
Assess renal involvement
Not specific for diagnosis of PAN
Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA 0050080
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody
Initial screen for connective tissue diseases
All ELISA results reported as Detected are further tested by IFA
ANA ELISA screen is designed to detect antibodies against dsDNA, histone, SS-A (Ro), SS-B (La), Smith, snRNP/Sm, Scl-70, Jo-1, centromere, and an extract of lysed HEp-2 cells
Results are not disease specific
ANA ELISA assays have been reported to have lower sensitivities for antibodies associated with nucleolar and specked ANA-IFA patterns
Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies 2002068
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay
Initial evaluation of suspected ANCA-associated vasculitis
If screen is positive, titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination
Not specific for diagnosis of PAN
Hepatitis B Virus Surface Antigen with Reflex to Confirmation 0020089
Method: Qualitative Chemiluminescent Immunoassay
Rule out concomitant chronic hepatitis B infection
Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay and IFA 2008403
Method: Semi-Quantitative Multiplex Bead Assay/Qualitative Indirect Fluorescent Antibody
Detect glomerular basement membrane (GBM) antibodies in suspected or established anti-GBM disease
Panel includes GBM antibody, IgG by multiplex bead assay and IFA
False positive results may occur due to reactivity against other chains of type IV collagen
Positive result should be confirmed by renal biopsy
Guidelines
American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed
Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, Al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N, Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010; 69(5): 798-806. PubMed
Ruperto N, Ozen S, Pistorio A, Dolezalova P, Brogan P, Cabral DA, Cuttica R, Khubchandani R, Lovell DJ, O'Neil KM, Quartier P, Ravelli A, Iusan SM, Filocamo G, Magalhães CS, Unsal E, Oliveira S, Bracaglia C, Bagga A, Stanevicha V, Manzoni SM, Pratsidou P, Lepore L, Espada G, Kone-Paut I, Paut IK, Zulian F, Barone P, Bircan Z, Maldonado Md, Russo R, Vilca I, Tullus K, Cimaz R, Horneff G, Anton J, Garay S, Nielsen S, Barbano G, Martini A, Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation. Ann Rheum Dis. 2010; 69(5): 790-7. PubMed
General References
Harrold LR, Liu NY. Polyarteritis nodosa presenting as pancytopenia: case report and review of the literature. Rheumatol Int. 2008; 28(10): 1049-51. PubMed
Kallenberg CG. The last classification of vasculitis. Clin Rev Allergy Immunol. 2008; 35(1-2): 5-10. PubMed
Pettigrew D, Teuber SS, Gershwin E. Polyarteritis nodosa. Compr Ther. 2007; 33(3): 144-9. PubMed
Medical Reviewers
Last Update: September 2016
